An observational multi-center study on type 2 diabetes treatment prescribing pattern and patient adherence to treatment

In 2021, the International Diabetes Federation (IDF) reported that the prevalence of diabetes in Pakistan was 9.6%, higher than the global average. However, adherence to treatment guidelines, e.g., American Diabetes Association and Pakistan Endocrine Society and prescription patterns for Oral anti-diabetes (OAD), is poorly understood in Pakistan. Therefore, this study aimed to examine the prescribing practices of anti-diabetic medications, an association of lifestyle modification with drugs prescribed, and their effectiveness in preserving ideal glycemic levels in diabetic patients undergoing treatment in tertiary care teaching hospitals in rural and urban Pakistan. In this cross-sectional study, data were collected from prescriptions of outpatient diabetic patients from different rural and urban tertiary care hospitals between October 2021 and February 2022. 388 participants were enrolled in the study for a detailed interview on prescription evaluation and glycemic control. The coinvestigators conducted an interview with the patient and used a pre-validated questionnaire to collect the data. The relationship between following treatment guidelines and clinical and demographic factors was found using chi-square tests for bivariate analyses. The study reported that out of 388, the mean ages of the patients were 48 ± 12.4, and the majority were female. It was observed that 60.1% and 66.5% have uncontrolled fasting and random blood glucose, respectively. The education level of the study participants was also below par to have a complete understanding of the medical condition and self-management therapy. Even though they were taking the right medications—an average prescription regimen included 5.08 medications—52.1% of the studied people had glycated haemoglobin (HbA1c) levels higher than the therapeutic threshold set by the International Diabetes Federation. In this modern era, it was observed that the prescribing trend was still focused on traditional therapeutic options Biguanides, sulfonylureas, and dipeptidyl peptidase-4 inhibitors were prescribed in 64.6% of the patients. A significant association was found between glycemic control and body mass index, adherence to lifestyle modifications, and the number of medications prescribed (p-value < 0.05). The study reveals that Pakistan's prescribing practices do not align with international and national guidelines, leading to a high prevalence of uncontrolled diabetes and widespread use of polypharmacy among patients. To address this issue, policymakers should prioritize establishing a comprehensive national diabetes action plan. Additionally, there is a pressing need to develop diabetes education and awareness programs emphasizing the importance of lifestyle modifications for effective diabetes management.


INTRODUCTION
Pakistan Endocrine Society (PES) guidelines for type 2 diabetes mellitus (T2DM) are based on available local, regional and international scientific evidence including special considerations to affordability and availability of medicines in Pakistan and consensus statements by Guidelines committee of PES.Diagnostic Criteria. 3,43-The above-mentioned tests should be performed in laboratory.

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For most non-pregnant T2DM patients a reasonable HbA1C goal is < 7%.

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For selected individual patients (short duration of diabetes, type 2 diabetes treated with lifestyle or metformin only, long life expectancy, or no significant cardiovascular disease) HbA1C goal such as 6.5%, maybe advised if this can be achieved without significant hypoglycemia.

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Less stringent A1C goals such as, 8% may be appropriate for patients with a history of severe hypoglycemia, limited life expectancy, advanced microvascular or macrovascular complications, extensive comorbid conditions, or longstanding diabetes.

Recommended-3.2.2: Self-monitoring of blood glucose (SMBG):
Frequency of SMBG will vary according to the treatment regimen and affordability of patients.Adherence to the prescribed frequency should be emphasized whenever possible.

RECOMMENDATION 4: Non pharmacological Management of Diabetes
Recommendation 4.1: Lifestyle modifications (LSM): 7 The key components of lifestyle therapy include:

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Set individualized target glycated hemoglobin (HbA1c) levels with the patient, and provide a level of care to achieve and maintain that target.

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Offer self-monitoring of blood glucose as an integral part of self-management, and agree when it should be performed and how it should be interpreted and acted upon.10][11] MNT should be started soon after diagnosis of T2DM by someone with training in nutrition therapy preferably by a registered dietitian (where available) and reviewed as per need.

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MNT should be aimed at achieving normoglycemia, providing adequate calorie intake.

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Simple sugars should be avoided.Food containing complex carbohydrate intake is recommended.

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PES -Guidelines for Management of Type 2 Diabetes Mellitus and Metabolic Syndrome ◼ High dietary fiber and whole grain containing foods should be encouraged.

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Non-calorie sweeteners (aspartame) may be used safely in moderate amounts.

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Lean protein, oily fish and vegetable consumption should be increased.

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Provide personalized diet plan in the form of printed diet charts while plate models can be used where necessary.Recommendation 4.1.3:Regular and adequate physical activity: [12][13][14] ◼ Physical Activity (PA), is an effective intervention in improving glycemic control, blood pressure and lipid levels in addition to improving sense of well-being.

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If patient has not been active at all, start slowly and increase activity over a period of time.Simple walk for at least 30 min, 5 days a week is enough in initial phases or simple aerobics that increase heart rate to 60-70% of maximum (Maximum Heart Rate = 220 -age in years).

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Minimal but significant changes in lifestyle like using stairs instead of taking elevators, parking car at a distance from workplace, keep walking while having conversation on phone etc. can bring significant change in activity status of a person.

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Plenty of water should be taken to avoid dehydration.In extremes of weather, indoor alternative exercises are favored.
Recommendation 4.1.4:Adequate Sleep: 14,15 ◼ All patients should be advised to sleep on average approximately 6-7 hours every night.◼ Six to 9 hours of sleep every night is associated with a reduction in cardiometabolic risk factors, whereas sleep deprivation aggravates insulin resistance, hypertension, hyperglycemia, and dyslipidemia and increases inflammatory cytokines.

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It should be emphasized that smoking is associated with an increase in cardiometabolic risk factors including insulin resistance, hypertension, hyperglycemia, and dyslipidemia.

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Counselling to quit smoking should be done at each visit Recommendation 4.1.6:Weight Reduction: 16,17 ◼ For weight reduction emphasis should be placed on lowering caloric intake and inducing weight loss for patients with type 2 diabetes who are overweight..

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A sustained weight loss of even 5 to 10 percent of initial body weight in overweight individuals can have a lasting beneficial impact on serum glucose, dyslipidemia, and hypertension.◼ Physical activity, diet, and behavioral modification are important components to accomplish weight loss.[20] ◼ Pharmacological therapy should be considered if one fails to achieve glycemic targets with nonpharmacological therapy (MNT & Physical activity) within target days.This should not be more than one month provided blood glucose is monitored and not significantly elevated.

RECOMMENDATION 5: Pharmacological Management of Diabetes
◼ Pharmacological treatment should be started right away if significant hyperglycemia is documented at time of diagnosis.

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The choice of diabetes therapies must be individualized based on attributes specific to both patients and the medications themselves in addition to the patient's cardiac, cerebrovascular, and renal status.

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The choice of therapy also considers ease of use and affordability.The therapeutic regimen should be as simple as possible to optimize adherence.

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Any of the selected regimes should be evaluated every three months with HbA1c and SMBG.

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Visit could be scheduled at shorter interval if there is Glycemic variability or hyper/hypoglycemia anticipated in initial management.

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If HbA1c is not available, SMBG and/or lab records can be helpful.

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People with diabetes should be assessed for possible side effects of drugs including hypoglycemic events, weight gain, fluid retentions, hepatic or renal impairment or cardiovascular risks.
◼ They should also be assessed for co morbidities, drug adherence and psychosocial issues.

Recommendation 5.1: Initial monotherapy:
◼ Metformin should be prescribed to all patients along with lifestyle modifications, irrespective of their baseline BMI, if there are no contraindications.(E high, R strong).

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If metformin is contraindicated or is not tolerated, GLP1 agonists, SGLT2 inhibitors, DPP4 Inhibitors, sulphonylureas or insulin can be used as alternative.

Recommendation 5.2: Initial Combination Therapy:
◼ In newly diagnosed people with diabetes presenting with signs and symptoms of hyperglycemia or having HbA1c >8.5%, a second oral agent or insulin should be considered along with metformin.Initial combination of sub maximal doses of antihyperglycemic agents produces better and quicker response than maximum doses of monotherapy.

Recommendation 5.3: Initial Insulin Therapy:
[20] Insulin as initial therapy is recommended for treatment of T2DM in people who are: ◼ Unable to tolerate oral hypoglycemics or non-insulin injectables.

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In situation when there is suspicion of patient having Type 1 vs. 2 and confirmation is not possible.

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Being treated for acute complications of diabetes (DKA, HHS).

Undergoing surgery.
◼ Unable to use oral hypoglycemics and non-insulin injectables due to allergies, renal or hepatic disorders in newly diagnosed patients with signs and symptoms of ketosis.

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Insulin can be categorized according to either duration of action ranging from rapid acting insulin to short acting, intermediate acting, long acting and very long acting insulin or their source as human or analogue insulin.The human insulin is less expensive than analogues, hence more affordable.

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The dose should be adjusted at regular intervals.Less expensive human insulin is beneficial in most of the cases particularly if comprehensive education about preventing, identifying and timely correction of hypoglycemia has been imparted.

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PES -Guidelines for Management of Type 2 Diabetes Mellitus and Metabolic Syndrome ◼ Required initial dose is 0.2 to 0.5 U/kg/day or 10 U/day.Obese people may need higher dose.Treatment should be graded to reach the targets and avoid unnecessary risk to patient (Hypoglycemia).General rule is start low and go slow if possible, in titration of Insulin.

Recommended approach to start insulin:
Step 1: In case of high fasting blood glucose (FBG), an intermediate acting human insulin or basal analogue insulin with a dose of 0.1 to 0.2U/kg or 10 U/day can be added at bedtime with the current oral therapy.The insulin dose may be titrated once or twice/week to reach the desired FBG.Analogue basal (ultralong acting) insulin can be given at fixed time of the day to have proper effect on fasting blood glucose.
Step 2: High post meal blood glucose should be controlled by bolus insulin, either by regular human insulin or by ultrashort acting insulin analogue with meal(s) and titrated every 48 to 72 hours to achieve the desired post-meal targets.
◼ Initial use of pre-mixed insulin regimens should ideally be avoided as it may not achieve the desired targets and put the patient at risk of fluctuating glycemic control.However, premixed insulin can be considered on individual basis where patients are unwilling to or unable to take basal bolus regimen.Insulin regimens like free mixing can also be considered for better management.These regimens require a vigilant follow up and patient's understanding of insulin use.

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Add GLP-1 receptor agonist to the basal insulin.The combination of GLP-1 receptor agonist and basal insulin is more effective in lowering glucose levels and has a lesser chance of weight gain and hypoglycemia as compared to the intensified insulin regimen.Also provides additional cardiovascular benefits to patient.However, cost is a major challenge in poor socioeconomic population.
Step 3: Intensive Insulin Therapy: ◼ If the HbA1c target is still not being met on basal insulin along with single injection of rapid-acting insulin before the largest meal of the day, proceed to a basal-bolus regimen with either 2 or 3 injections of rapid-acting insulin before each meal i.e. before breakfast, lunch and dinner.Insulin regimens like split mix and modified split mix can also be considered for better management.These regimens require a vigilant follow up and patient awareness about risk of hyper/hypoglycemia.These regimens require very intensive patient education..

RECOMMENDATION 6: Hypertension and Diabetes
High blood pressure is recognized as a major risk factor for CVD and CKD.

Recommendation 6.1.1: Monitoring of Blood pressure:
◼ Blood pressure should be measured at every clinic visit.Patients newly diagnosed with systolic blood pressure of ≥ 140 mmHg or a diastolic blood pressure of ≥ 90 mmHg should have blood pressure confirmed on a subsequent day.

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Blood pressure measurement should be measured by trained personnel.Standard protocol for blood pressure measurement must be followed i.e., in the seated position, with feet on the floor and arm supported at heart level, after 5min of rest.Cuff size should be appropriate for the upper arm circumference.

Recommendation 6.1.2: Blood Pressure (Targets):
◼ Systolic blood pressure (SBP) target should be <140 mmHg and diastolic blood pressure should be <90 mmHg in all people with diabetes and hypertension.There is limited evidence for the benefits of further lowering systolic blood pressure or diastolic blood pressure targets.

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If complications are present (additional risk factors and small vessel disease, particularly albuminuria), a tighter target may be appropriate.

Recommendation 6.1.3: Therapeutic Management Strategies:
◼ Patients with confirmed blood pressure readings of >140/90mmHg should be promptly initiated pharmacological therapy, in addition to dietary changes (e.g.DASH Diet/ Sodium Intake) and life style modifications.Therapy must be titrated to achieve the desired goals.

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Lifestyle modifications consists of reducing excess body weight, increasing consumption of fruits and vegetables (4-5 servings per day), consuming low-fat dairy products (2-3 servings per day) and increasing activity levels.◼ Sodium intake is restricted, the restriction should be the same for people with and without diabetes.The simplest strategy is not to add table salt to meals.

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For patients with diabetes and hypertension, ACE inhibitor/ARBs should be considered as initial therapy.

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If target blood pressure level is not achieved after 2-3 months, addition of either a calcium channel blocker, β-blocker or thiazide diuretic may be considered.

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Initial combination therapy may be needed when SBP is >20 mmHg and/or DBP is >10 mmHg above target, but this may vary with ethnicity and age.

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If ACE inhibitors, ARBs, or diuretics are used, serum creatinine and serum potassium levels should be monitored after10 days and then at 6th week.Ideally monitor creatinine every six to twelve months if it does not exceed more than 30% from its baseline.

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It is common to have an acute rise in serum creatinine of up to 30% within 2-5 days of initiating an ACEI or ARB, especially if the patient has CKD/CHF.These can be safely continued in these patients if the creatinine subsequently stabilizes at the higher level.

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If blood pressure remains uncontrolled despite good compliance to optimal doses of at least three antihypertensive agents of different class, one of which should be a diuretic, an evaluation for secondary hypertension should be considered.

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Additionally, antihypertensive effects of other medication such as SGLT 2 inhibitor, GLP Agonist and statins should be taken into account specially when starting them during same visit.

RECOMMENDATION -7: Dyslipidemia and Diabetes:
High blood lipid levels are considered as a major cardiovascular risk factor and particularly high LDL cholesterol.All people with T2D and established CVD should start treatment with a statin (secondary prevention).
All patients type 2 diabetes should have dilated eye examination by an ophthalmologist at diagnosis or at first visit to the clinic.

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If the screening for retinopathy is positive or if the patient has unexplained reduced visual acuity with or without retinopathy, the individual should be referred to an ophthalmologist.

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If no sign of retinopathy is present repeat examination annually.If retinopathy is present, frequency of examination should be suggested by ophthalmologist.

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Aspirin can safely be prescribed in patients with retinopathy as it does not increase the chances of retinal hemorrhage unless there is some other contraindication.

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All patients with type 2 diabetes should be screened for microalbuminuria annually.

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Measure serum creatinine every six months to calculate eGFR once albuminuria is detected and/or when other risk factors are present (e.g., hypertension).

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Uncontrolled diabetes or hypertension, fever, infection, recent exercise or congestive cardiac failure may result in proteinuria without kidney disease.

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Two readings three months apart should be taken before making a diagnosis of nephropathy.

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Diabetic kidney disease (DKD, diabetic nephropathy) is identified when eGFR is <60 mL/min/1.73m2 and/or albuminuria ≥30 mg/g creatinine ◼ Persistent albuminuria requires treatment with an ACE inhibitor or an ARB even in normotensive people after taking baseline serum creatinine and potassium.

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For patients with type 2 diabetes and chronic kidney disease, consider use of a sodium-glucose cotransporter 2 inhibitor or glucagon-like peptide 1 receptor agonist which has shown to reduce risk of chronic kidney disease progression, cardiovascular events, or both.

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In non-pregnant patients with diabetes and hypertension the first line anti hypertensives are ACEI or ARBs.Combination of these drugs with each other should be avoided due to increased incidence of hyperkalemia ◼ In selected high-risk patient, Serum creatinine and potassium should be rechecked after 10 days and 6 weeks in cases of newly prescribed ACEI/ARBs.It is common to have an acute rise in serum creatinine of up to 30% within 2-5 days of initiating an ACEI/ARB.These can be safely continued in patients if the creatinine subsequently stabilizes at the higher level.

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Good metabolic control is essential to delay the progression of nephropathy.
◼ Dietary proteins should be restricted to 0.8mg/kg / day if macroalbuminuria is present ◼ People should be referred to a nephrologist when they have DKD stage 4 or 5 (eGFR<30 mL/min/1.73m2) or unexplained heavy proteinuria with or without hematuria in the absence of retinopathy or with short disease duration (e.g., other causes of renal disease) or with a rapid fall in the eGFR.

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All people with diabetes require thorough assessment for peripheral neuropathy on presentation.Frequency of follow up assessment depends on presence of neuropathy and/or loss of protective sensations.

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Most common presenting complaints are pain, burning and tingling sensations.Almost 50% of patients may be asymptomatic.Identifying these insensate feet is important for prevention of foot ulcers.

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This assessment includes testing with 10 grams monofilament and any of the additional tests for pin prick, vibration or temperature sense to identify if the foot is at risk ◼ Medication with proven efficiency include duloxetine, gabapentin or pregabalin can be given as initial treatment.Additionally amitriptyline and nortriptyline can be offered with caution due to side effect profile.

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Other Secondary causes of Neuropathy must be evaluated in case of new onset neuropathy.In patients presenting with atypical or painful neuropathy, other causes should be excluded like, vit B12 deficiency, Renal disease, Vasculitis, thyroid disease, vitamin D Deficiency, neurotoxic medications, chronic inflammatory demyelinating neuropathy etc., by obtaining relevant tests.

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Take history regarding symptoms of autonomic neuropathy involving cardiovascular system, gastrointestinal tract including gastroparesis, genitourinary system including erectile dysfunction (ED) and offer appropriate treatment.

RECOMMENDATIONS 10: Screening for Macrovascular Disease Recommendations 10.1: Screening for Coronary Artery Disease:
◼ Screen for coronary artery disease (CAD) when the patient has typical or atypical symptoms.(Chest pain, shortness of breath, orthopnea, paroxysmal nocturnal dyspnea etc.) ◼ Assess cardiovascular risk factors in all T2DM patients annually (Hypertension, dyslipidemia, smoking, obesity, family history of premature CVD etc.).Special attention should be paid to patient presenting with microvascular complication such as retinopathy / microalbuminuria as they might have silent macrovascular complications well.

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Offer aspirin and statin to patients who are at increased risk of CVD.

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Offer ACE inhibitors or ARBS to hypertensive diabetic patients with nephropathy.

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TZDs should be avoided in symptomatic patients with CHF Overview:

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The choice of pharmacological agent must be individualized, based on attributes specific to both patients and the medications.

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The choice of therapy also depends on the patient's age, BMI, duration of disease, glycemic status, risk of hypoglycemia, cardiac, cerebrovascular, renal function and financial status

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The choice of therapy should take into consideration ease of use and availability.The therapeutic regimen should be as simple as possible to optimize adherence.

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Comorbidities must be managed for comprehensive care, including management of lipid and blood pressure abnormalities and treatment of other related conditions.◼ Any of the selected regimes should be evaluated every three months with HbA1c and SMBG.If HbA1c is not available, SMBG and/or lab records can be helpful.Patients should be assessed for possible side effects of drugs, including hypoglycemic events, weight gain, fluid retention, hepatic or renal impairment or cardiovascular risks.They should also be assessed for co morbidities, drug adherence and psychosocial issues. 1◼ Metformin should be prescribed to all patients along with lifestyle modifications, irrespective of their baseline BMI, if there are no contraindications. 2If metformin is contraindicated or is not tolerated, GLP1 agonists or SGLT2 inhibitors can be prescribed as preferred agents.DPP4 Inhibitors, sulphonylureas or alpha glucosidase inhibitors can be used as alternatives. 3

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In newly diagnosed patients with T2DM presenting with signs and symptoms of hyperglycemia and having an HbA1c >8.5%, a second oral agent or insulin should be considered along with metformin.[5]

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Metformin is an insulin-sensitizer, which causes reduction in insulin resistance and a significant decrease in plasma fasting insulin levels.Metformin monotherapy can reduce HbA1c by 1.1%. 6

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It also provides benefits of weight stability or slight weight reduction. 7◼ It is generally well tolerated.Most commonly reported side effects are anorexia, nausea, diarrhea and a metallic taste.These effects can be minimized if metformin is taken with meals.◼ Lactic acidosis is the only serious side effect.However, its risk incidence is extremely low. 8◼ It is contraindicated in CKD Stage 4 and 5 (eGFR<30).9If eGFR is not available metformin should be discontinued at serum creatinine>1.5mg/dl in men and > 1.4 mg/dl in women.

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Metformin is excreted by the kidneys.The reduction in renal clearance of metformin is considered as an important risk factor for lactic acidosis it should be started at a low dose and titrated upwards until the required glycemic targets are achieved or another oral agent is added in regime.

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It may also be associated with Vit B12 deficiency in some cases with long term use.

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The maximum dose is up to 2550 mg in divided doses.It should be started at a low dose, typically 500mg twice daily, with upward titration if desirable control of hyperglycemia is not achieved.The drug is well tolerated.

SGLT2 Inhibitors:
◼ Sodium-glucose co-transporters (SGLT2) are present in proximal tubules of kidneys.Kidneys filter glucose freely, 90% of which is reabsorbed in the proximal tubules by the action of SGLT2.◼ SGLT2 inhibitors lower HBA1c by 0.7-1%. 10Available SGLT2 agents in Pakistan are dapagliflozin (5 and 10 mg) and empagliflozin (10 and 25 mg).◼ Dose of dapagliflozin is 10 mg daily, but it is recommended to start with 5mg initially.Dose of empagliflozin is 10 mg daily, but higher dose of 25 mg daily can be used.

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The main side effects are increased incidence of genital mycotic infections and urinary tract infections.

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Efficacy of SGLT2i is decreased in chronic kidney disease and is contraindicated in patients with eGFR less than <30. 2,3,10P 1 agonists ◼ Glucagon-like peptide 1 (GLP-1) is known for the 'incretin effect', which results in a glucose dependent increase in insulin secretion and suppression of glucagon secretion from the pancreas.bedtime with the current oral therapy.18,19 ◼ To prevent hypoglycemia, it is advised to initiate insulin with a starting dose of 0.2 units/kg, while adjusting the dose by increasing 2 units every 3 days based on the fasting blood glucose levels until the desired target is achieved.18,19 ◼ SMBG should be done at least twice daily, usually before breakfast and before bedtime, but more frequent SMBG is recommended to meet goals of the therapy.19,20 If only Post-Prandial Blood Glucose Levels are High: The following options can be considered ◼ Continue the bedtime NPH injection and add a second injection of NPH before breakfast at a dose of 0.2 units per kg. 19,20Metformin, SGLT2 inhibitors, DPP-4 may need to be continued.Addition of GLP-1 or SGLT2 inhibitors may help to improve control in patients with suboptimal glycemic levels requiring higher insulin doses, and may reduce the amount of insulin required in these patients. 20Add rapid-acting or short-acting insulin before the largest meal of the day.Initiate with a starting dose of approximately 4 units, 18 while adjusting the dose by 2 units every 3 days until the desired target is achieved. 21

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Add once daily dose of Degludec+Aspart (70/30) with largest meal of the day.◼ Switch to pre-mixed or free-mix (R and NPH) insulin twice a day before breakfast and dinner.

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Add GLP-1 receptor agonist to the basal insulin.The combination of GLP-1 receptor agonist and basal insulin is more effective in lowering glucose levels and has a lesser chance of weight gain and hypoglycemia as compared to the intensified insulin regimen.However, cost is a major challenge in low socioeconomic countries like Pakistan.

Intensive Insulin Therapy:
If the HbA1c target is still not being met on basal insulin along with single injection of rapid-acting insulin before the largest meal of the day, proceed to a basal-bolus regimen with either 2 or 3 injections of rapid-acting insulin before each meal i.e. before breakfast, lunch and dinner. 21ample of Intensive insulin regimen by using rapid acting insulin or intermediate or long acting insulin in 70 kg man with type 1 diabetes.Assume he is consuming 75g carbohydrate at breakfast, 60g at lunch, and 90g at dinner.

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The dose of rapid acting analogs can be raised by 1 or 2 unit if extra carbohydrate (15-30g) is ingested or if premeal blood glucose is >170mg/dl.

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The rapid acting insulin can be mixed in the same syringe with NPH insulin.

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Insulin glargine or insulin detemir must be given as a separate injection.

2. 4 - 6 Recommendation - 3 . 2 :
Asymptomatic individuals with a single abnormal test should have the same test repeated to confirm the diagnosis.On the other hand, if a patient has discordant results in two tests, the test result that is above the diagnostic cut point should be repeated.Symptomatic individuals do not need repetition of the abnormal test.RECOMMENDATION -3: Glycemic Targets &Assessment of Glycemic targets Recommendation No 3.1: Glycemic Targets: Assessment of Glycemic targets: Recommendation -3.2.1: HbA1c: ◼ Perform the HbA1C test at least two times a year in patients who have stable glycemic control.◼ Perform the HbA1C test quarterly in patients whose therapy has changed or who are not meeting glycemic goals.

◼Recommendation 4 . 1 . 1 :
Diabetes self-management education (DSME) ◼ Medical nutrition therapy (MNT) comprising of healthy eating patterns, ◼ Regular and adequate physical activity, ◼ Sufficient amount of sleep, ◼ Smoking cessation with avoidance of all tobacco products.Diabetes self-management education: ◼ Persons with T2D must improve their lifestyle from the time of diagnosis to reach the metabolic targets as soon as possible.This can be achieved best assisted with an effective education program ◼ Patients with T2D should be referred to a diabetes education program at the time of diagnosis and the program should be conducted by a trained diabetes educator (where available).

Recommendation 4 . 1 . 5 :
Smoking Cessation:◼ Smoking cessation is another important component of lifestyle therapy and involves avoidance of all tobacco products including pan, gatka, huqqa, niswar, shisha and e-cigarettes.